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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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La hematopoyesis de la médula ósea impulsa la progresión de la esclerosis múltiple

Kaibin Shi1, Handong Li2, Ting Chang3

  • 1Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China; Center for Neurological Diseases, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Cell
|June 16, 2022
PubMed
Resumen

En la esclerosis múltiple (EM), las células madre de la médula ósea se desplazan hacia la producción de mieloides, aumentando las células inflamatorias que entran en el sistema nervioso central (SNC). Dirigirse a la médula ósea puede ofrecer nuevos tratamientos para la EM.

Palabras clave:
células T autoreactivasmédula óseaesclerosis múltipleLa mielopoyesisLa neuroinflamación

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Área de la Ciencia:

  • Inmunología
  • La neurociencia
  • Hematología

Sus antecedentes:

  • La esclerosis múltiple (EM) es una enfermedad autoinmune mediada por células T que afecta al sistema nervioso central (SNC).
  • No se comprende bien el papel de las células madre y progenitoras hematopoyéticas de la médula ósea (HSPC) en la patogénesis de la EM.
  • Se sabe que los HSPC responden a la activación inmune.

Objetivo del estudio:

  • Investigar la interacción entre las células T autorreactivas y las células HSPC de la médula ósea en la EM.
  • Explorar los mecanismos que impulsan la mielopoyesis aberrante en la médula ósea de los pacientes con EM.
  • Determinar si la orientación hacia el nicho de la médula ósea puede afectar la inflamación del SNC en la EM.

Principales métodos:

  • Análisis del sesgo del linaje HSPC y la expansión de las células T en pacientes con EM.
  • El rastreo del linaje en la encefalomielitis autoinmune experimental (EAE), un modelo de ratón de EM.
  • Investigación de las vías de migración celular (por ejemplo, CXCR4) y de los ejes de señalización (por ejemplo, CCL5-CCR5) en la médula ósea.

Principales resultados:

  • Los HSPC de médula ósea en pacientes con EM muestran un sesgo de linaje mieloide con expansión de células T clonales.
  • Los ratones EAE presentan un aumento de la mielopoyesis de la médula ósea, produciendo neutrófilos y monocitos Ly6Chigh que se infiltran en el SNC.
  • Las células T reactivas a la mielina migran a la médula ósea a través de CXCR4, y el eje CCL5-CCR5 impulsa la mielopoyesis, exacerbando la inflamación del SNC y la desmielinización.

Conclusiones:

  • La mielopoyesis anormal de la médula ósea, impulsada por las interacciones de las células T, contribuye a la patología del SNC en la EM.
  • El nicho de la médula ósea juega un papel crítico en la patogénesis de la EM.
  • Dirigirse al microambiente de la médula ósea presenta una estrategia terapéutica potencial para la EM y otras enfermedades autoinmunes.